Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis

Respir Res. 2015 Sep 15;16(1):105. doi: 10.1186/s12931-015-0264-9.


Rationale: Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma.

Method: Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points.

Results: Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils.

Conclusion: In summary, we were able to show that uridine has potent anti-inflammatory and anti-fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bleomycin
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Line, Tumor
  • Collagen / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice, Inbred C57BL
  • Pneumonia / chemically induced
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Uridine / pharmacology*


  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Transforming Growth Factor beta
  • Bleomycin
  • Collagen
  • Uridine